Sucralfate has complex interactions with both the luminal and mucosal environments of the stomach. To study potential mechanisms of action, the effects of sucralfate on mucus synthesis and secretion were investigated by utilizing an in vitro system comprised of a human gastric carcinoma cell line, AGS. In this study, AGS cell synthesis and secretion of the major components of mucus, lipid and glycoproteins, were estimated using metabolic labeling methods. The results showed that sucralfate preferentially stimulated the synthesis and secretion of phosphatidyl-choline and triglyceride, but did not alter the synthesis and secretion of glycoprotein. In addition, indomethacin blocked the sucralfate-induced lipid synthesis and secretion, possibly implicating prostaglandins as mediators of some of the drug's cytoprotective actions. In part, this work supports the proposed role of sucralfate's stimulatory effects on synthesis and secretion of lipids as contributing to enhancement of the mucosal barrier in ulcer treatment. Additionally, this study demonstrated that the AGS cell line is useful in vitro for studying the gastric epithelial cell mucus synthesis and secretion.